Swit RAPS Annual Conf 2010 Biosimilars by 9o8G37


The New U.S. Pathway

RAPS Annual Conference

          San Jose
       October 25, 2010

    Michael A. Swit, Esq.
       Vice President
             Standard Disclaimers

 Views expressed here are solely mine and do not
 reflect those of my firm or any of its clients.

 This presentation supports an oral briefing and
 should not be relied upon solely on its own to
 support any conclusion of law or fact.

                            The Past
 Biologics approved under Public Health Services Act –
 no abbreviated pathway
   Precursor? -- Comparability Guidance, April 1996
 NDAs -- for few biologics (e.g., HGH, insulin) – were
   No set criteria on appropriate data set to support approval
   Evaluated on a case by case basis
 Therapeutic Biologics – transferred from CBER to

 Lynchpin to traditional Waxman-Hatch generic
 approval process – depends on:
     Pharmaceutical “equivalents” – active ingredient, dosage form,
      strength, etc., must be SAME
     Highly unlikely with Biosimilars –
        Characterization – still a challenge even for the innovators –

         clinical trials may be needed to show comparability after process
             Chances of “equivalence” conclusions faint as even a single amino
              acid can throw off conclusion (e.g., HGH)
             Lovenox – only 70% characterized (but, is under an NDA and
              recently approved under an ANDA)

                       Bioequivalence …
   Janet Woodcock, Director, Center for Drugs (before Congress,
    March 2007):
       “there is general recognition that the idea of sameness, as the term
        is used in the generic drug approval process under the Federal
        Food, Drug, and Cosmetic (FD&C) Act and applied to small
        molecules, will not usually be appropriate for more structurally
        complex molecules of the type generally licensed as biological
        products under the Public Health Service Act.”

                           Substitutability …
 Substitution -- core of classic Generic Industry Business
     Depends on therapeutic equivalence
     Allows for minimal sales forces
     Drives pricing down -- multiple generics common – the generic
      becomes a commodity
 Biosimilar world –
   Substitution – aka “interchangeability” -- may evolve, but on a very,
      very limited basis
        Woodcock – must be able to handle repeated brand/follow-in switching
           without adverse events
          Thus, business model will not be multiple generics & not a commodity
   Without interchangeability, the Biosimilar     IS a branded drug

 What Hath Health Care Reform Wrought?
 Biologics Price Competition & Innovation Act of 2009
   Creates an abbreviated pathway for “biosimilar” versions of
    biologics, but gives FDA great flexibility/discretion in how it
    implements statute
 Key features
   Abbreviated pathway created under the Public Health Service
    Act (PHSA) by adding Subsection (k) to Section 351 of the
   Exclusivity – 12 years for new biologics
   Complex handling of patents
   FDA – flexibility granted in how it regulates biosimilars
What’s Required for a Biosimilar Application?
 Must be biosimilar to Reference Product, by including:
   Analytical studies to show your product is Highly similar to
    the Reference Product (RP) – i.e, the Biosimilar has no
    clinically meaningful differences from the RP in terms of
    safety, purity and potency, notwithstanding minor differences
    in clinically inactive components; and
   Animal Studies – including toxicity studies; and
   “A clinical study or studies” -- including assessment of
    immunogenicity and pharmacokinetics or pharmacodynamics
      to show safe, pure and potent
      in 1 (one) or more appropriate conditions of use for which the RP
       is licensed and intended to be used

      Required for a Biosimilar Application …
 Must use same mechanism(s) of action – if the MOA is
  known for the RP
 Conditions of use in labeling have to be previously
  approved for the RP
 Must match RP as to:
   Route of administration
   Dosage form
   Strength
 Facility in which manufactured, processed, packed or
  held – must meet standards designed to assure the
  biosimilar continues to be: Safe. Pure. Potent.
 FDA – can decide any of the above are unnecessary      9
 Not required – 351(k)(2)(B)
 To prove interchangeability – 351(k)(4)
   Drug must be biosimilar to RP
   BP “can be expected to produce the same clinical result” as
    the RP “in any given patient”
   If BP is administered more than once to patient, the risk in
    terms of safety or diminished efficacy of switching between
    the BP and the RP is “not greater than the risk of using the
    RP” without switching
      How to study – multiple switch study

                 Miscellaneous Rules
 Only One RP per BP application – 351(k)(5)(A)
 Reviewing division – same as handled the RP – 351(k)(5)(B)
 REMS – authority under FDAAA applies to Biosimilars –
 Biologics approved under Section 505 of Federal Food,
  Drug, and Cosmetic Act as New Drug Applications
   Can still be filed as NDAs
   However, if there is a PHSA licensed biologic, a biosimilar
    application must be filed as a 351(k) application
   Ten years after enactment – all NDAs for biologics are deemed
    approved under Section 351 of PHSA
                      Miscellaneous …
 Guidances
   Not required prior to approval of a biosimilar application
   Regulations – also not mandated
   Product Class Specific Guidances
      Can be issued
      FDA – can issue one saying that the science is not sufficient to
       allow a biosimilar application
         Later can be reversed
         Absence of such a guidance does not mandate that a biosimilar
          application can be approved
 Pediatrics – all the rules and benefits under FDAAA for
  both doing studies and pediatric exclusivity apply to
         Uncertainty … Runs Rampant
 How will FDA implement BPCIA?
   Teva – is pursuing full BLAs as of now –
   Leah Christl, Ph.D. – Acting Director in CDER for
 FDA – Public Meeting on Biosimilars
   Oct. 5, 2010 Federal Register – 75 Fed. Reg. 61497
   Nov. 2 & 3, 2010 in Maryland (also will be webcast)

             Input FDA Seeks at Hearing
 Scientific and technical information on how to
  implement the statute
 “Extra-statutory Issues”
   Pharmacovigilance
   Common or usual names
   Safeguards on unsafe substitution
   Bridging data needed when comparing a BP to an RP after
    prior studies done on BP vs. a non-U.S. biologic (e.g., in EU)

 Call, e-mail, fax or write:

   Michael A. Swit, Esq.
       Vice President
The Weinberg Group Inc.
  1422 Caminito Septimo
Cardiff by the Sea, CA 92007
    Phone 760.452.6568
     Fax 760.454.2979
     Cell 760.815.4762

                                  About your speaker…
Michael A. Swit, Esq., is a Vice President at THE WEINBERG GROUP, where he develops and ensures the
execution of a broad array of regulatory and other services to drug and biologics clients seeking to market products in
the United States. His expertise includes FDA development strategies, compliance and enforcement initiatives, recalls
and crisis management, submissions and related traditional FDA regulatory activities, labeling and advertising, and
clinical research efforts.

Mr. Swit has been addressing critical FDA legal and regulatory issues since 1984. His multi-faceted experience
includes serving for three and a half years as corporate vice president, general counsel and secretary of Par
Pharmaceutical, a prominent, publicly-traded, generic drug company and, thus, he brings an industry and commercial
perspective to his work with FDA-regulated companies. Mr. Swit then served for over four years as CEO of
FDANews.com, a premier publisher of FDA regulatory newsletters and other specialty information products for the
FDA-regulated community. His private FDA regulatory law practice has included service as Special Counsel in the
FDA Law Practice Group in the San Diego office of Heller Ehrman White & McAuliffe and with the Food & Drug
Law practice at McKenna & Cuneo, both in the firm’s Washington office and later in San Diego. He first practiced
FDA regulatory law with the D.C. office of Burditt & Radzius.

Mr. Swit has taught and written on a wide variety of subjects relating to FDA law, regulation and related commercial
activities, including, since 1989, co-directing a three-day intensive course on the generic drug approval process and
editing a guide to the generic drug approval process, Getting Your Generic Drug Approved. A former member of the
Food & Drug Law Journal Editorial Board, he also has been a prominent speaker at numerous conferences sponsored
by such organizations as RAPS, FDLI, and DIA. A magna cum laude graduate of Bowdoin College, he received his
law degree from Emory University Law School and is a member (inactive) of the California, D.C. and Virginia bars.


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